rs1057079

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004958.4(MTOR):c.4731G>A(p.Ala1577Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,390 control chromosomes in the GnomAD database, including 413,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 29032 hom., cov: 31)

Exomes 𝑓: 0.72 ( 384315 hom. )

Consequence

MTOR
NM_004958.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.869

Variant links:

Genes affected

MTOR (HGNC:3942): (mechanistic target of rapamycin kinase) The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]

MTOR links:

MTOR-AS1 (HGNC:40242): (MTOR antisense RNA 1)

MTOR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-11145001-C-T is Benign according to our data. Variant chr1-11145001-C-T is described in ClinVar as [Benign]. Clinvar id is 516654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11145001-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.869 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTOR	NM_004958.4 link	c.4731G>A	p.Ala1577Ala	synonymous_variant	Exon 33 of 58	ENST00000361445.9	NP_004949.1	P42345

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9 link	c.4731G>A	p.Ala1577Ala	synonymous_variant	Exon 33 of 58	1	NM_004958.4	ENSP00000354558.4		P42345

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85698

AN:

151880

Hom.:

29024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.804

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.609

GnomAD3 exomes

AF:

0.686

AC:

172411

AN:

251352

Hom.:

62071

AF XY:

0.692

AC XY:

93952

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.728

Gnomad ASJ exome

AF:

0.581

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.721

Gnomad NFE exome

AF:

0.741

Gnomad OTH exome

AF:

0.690

GnomAD4 exome

AF:

0.718

AC:

1049597

AN:

1461392

Hom.:

384315

Cov.:

AF XY:

0.717

AC XY:

521497

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.835

Gnomad4 SAS exome

AF:

0.654

Gnomad4 FIN exome

AF:

0.721

Gnomad4 NFE exome

AF:

0.742

Gnomad4 OTH exome

AF:

0.683

GnomAD4 genome

AF:

0.564

AC:

85707

AN:

151998

Hom.:

29032

Cov.:

AF XY:

0.567

AC XY:

42106

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.593

Gnomad4 EAS

AF:

0.804

Gnomad4 SAS

AF:

0.640

Gnomad4 FIN

AF:

0.720

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.611

Alfa

AF:

0.689

Hom.:

63961

Bravo

AF:

0.544

Asia WGS

AF:

0.683

AC:

2376

AN:

3478

EpiCase

AF:

0.732

EpiControl

AF:

0.734

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.6

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over